(-)-Epigallocatechin Gallate Reduces Platelet-Derived Growth Factor-BB-Stimulated Interleukin-6 Synthesis in Osteoblasts: Suppression of SAPK/JNK

We previously showed that the mitogen-activated protein (MAP) kinase superfamily, p44/p42 MAP kinase, p38 MAP kinase, and stress-activated protein kinase (SAPK)/c-Jun N-terminal (JNK), positively plays a part in the platelet-derived growth factor-BB- (PDGF-BB-) stimulated synthesis of interleukin-6...

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Main Authors: Shinji Takai, Rie Matsushima-Nishiwaki, Seiji Adachi, Hideo Natsume, Chiho Minamitani, Jun Mizutani, Takanobu Otsuka, Haruhiko Tokuda, Osamu Kozawa
Format: Article
Language:English
Published: Wiley 2008-01-01
Series:Mediators of Inflammation
Online Access:http://dx.doi.org/10.1155/2008/291808
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author Shinji Takai
Rie Matsushima-Nishiwaki
Seiji Adachi
Hideo Natsume
Chiho Minamitani
Jun Mizutani
Takanobu Otsuka
Haruhiko Tokuda
Osamu Kozawa
author_facet Shinji Takai
Rie Matsushima-Nishiwaki
Seiji Adachi
Hideo Natsume
Chiho Minamitani
Jun Mizutani
Takanobu Otsuka
Haruhiko Tokuda
Osamu Kozawa
author_sort Shinji Takai
collection DOAJ
description We previously showed that the mitogen-activated protein (MAP) kinase superfamily, p44/p42 MAP kinase, p38 MAP kinase, and stress-activated protein kinase (SAPK)/c-Jun N-terminal (JNK), positively plays a part in the platelet-derived growth factor-BB- (PDGF-BB-) stimulated synthesis of interleukin-6 (IL-6), a potent bone resorptive agent, in osteoblast-like MC3T3-E1 cells while Akt and p70 S6 kinase negatively regulates the synthesis. In the present study, we investigated whether (-)-epigallocatechin gallate (EGCG), one of the major green tea flavonoids, affects the synthesis of IL-6 in these cells and the mechanism. EGCG significantly reduced the IL-6 synthesis and IL-6 mRNA expression stimulated by PDGF-BB, EGCG reduced the PDGF-BB-stimulated IL-6 synthesis also in primary-cultured osteoblasts. EGCG had no effect on the levels of osteocalcin and osteoprotegerin in MC3T3-E1 cells. The PDGF-BB-induced autophosphorylation of PDGF receptor β was not suppressed by EGCG. The PDGF-BB-induced phosphorylation of p44/p42 MAP kinase and p38 MAP kinase was not affected by EGCG. On the other hand, EGCG markedly suppressed the PDGF-BB-induced phosphorylation of SAPK/JNK. Finally, the PDGF-BB-induced phosphorylation of Akt and p70 S6 kinase was not affected by EGCG. These results strongly suggest that EGCG inhibits the PDGF-BB-stimulated synthesis of IL-6 via suppression of SAPK/JNK pathway in osteoblasts.
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spelling doaj-art-e6ae2c1af7334cacb6e0541db863dab72025-02-03T01:21:21ZengWileyMediators of Inflammation0962-93511466-18612008-01-01200810.1155/2008/291808291808(-)-Epigallocatechin Gallate Reduces Platelet-Derived Growth Factor-BB-Stimulated Interleukin-6 Synthesis in Osteoblasts: Suppression of SAPK/JNKShinji Takai0Rie Matsushima-Nishiwaki1Seiji Adachi2Hideo Natsume3Chiho Minamitani4Jun Mizutani5Takanobu Otsuka6Haruhiko Tokuda7Osamu Kozawa8Department of Pharmacology, Gifu University Graduate School of Medicine, Gifu 501-1194, JapanDepartment of Pharmacology, Gifu University Graduate School of Medicine, Gifu 501-1194, JapanDepartment of Pharmacology, Gifu University Graduate School of Medicine, Gifu 501-1194, JapanDepartment of Pharmacology, Gifu University Graduate School of Medicine, Gifu 501-1194, JapanDepartment of Pharmacology, Gifu University Graduate School of Medicine, Gifu 501-1194, JapanDepartment of Orthopedic Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya 467-8601, JapanDepartment of Orthopedic Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya 467-8601, JapanDepartment of Pharmacology, Gifu University Graduate School of Medicine, Gifu 501-1194, JapanDepartment of Pharmacology, Gifu University Graduate School of Medicine, Gifu 501-1194, JapanWe previously showed that the mitogen-activated protein (MAP) kinase superfamily, p44/p42 MAP kinase, p38 MAP kinase, and stress-activated protein kinase (SAPK)/c-Jun N-terminal (JNK), positively plays a part in the platelet-derived growth factor-BB- (PDGF-BB-) stimulated synthesis of interleukin-6 (IL-6), a potent bone resorptive agent, in osteoblast-like MC3T3-E1 cells while Akt and p70 S6 kinase negatively regulates the synthesis. In the present study, we investigated whether (-)-epigallocatechin gallate (EGCG), one of the major green tea flavonoids, affects the synthesis of IL-6 in these cells and the mechanism. EGCG significantly reduced the IL-6 synthesis and IL-6 mRNA expression stimulated by PDGF-BB, EGCG reduced the PDGF-BB-stimulated IL-6 synthesis also in primary-cultured osteoblasts. EGCG had no effect on the levels of osteocalcin and osteoprotegerin in MC3T3-E1 cells. The PDGF-BB-induced autophosphorylation of PDGF receptor β was not suppressed by EGCG. The PDGF-BB-induced phosphorylation of p44/p42 MAP kinase and p38 MAP kinase was not affected by EGCG. On the other hand, EGCG markedly suppressed the PDGF-BB-induced phosphorylation of SAPK/JNK. Finally, the PDGF-BB-induced phosphorylation of Akt and p70 S6 kinase was not affected by EGCG. These results strongly suggest that EGCG inhibits the PDGF-BB-stimulated synthesis of IL-6 via suppression of SAPK/JNK pathway in osteoblasts.http://dx.doi.org/10.1155/2008/291808
spellingShingle Shinji Takai
Rie Matsushima-Nishiwaki
Seiji Adachi
Hideo Natsume
Chiho Minamitani
Jun Mizutani
Takanobu Otsuka
Haruhiko Tokuda
Osamu Kozawa
(-)-Epigallocatechin Gallate Reduces Platelet-Derived Growth Factor-BB-Stimulated Interleukin-6 Synthesis in Osteoblasts: Suppression of SAPK/JNK
Mediators of Inflammation
title (-)-Epigallocatechin Gallate Reduces Platelet-Derived Growth Factor-BB-Stimulated Interleukin-6 Synthesis in Osteoblasts: Suppression of SAPK/JNK
title_full (-)-Epigallocatechin Gallate Reduces Platelet-Derived Growth Factor-BB-Stimulated Interleukin-6 Synthesis in Osteoblasts: Suppression of SAPK/JNK
title_fullStr (-)-Epigallocatechin Gallate Reduces Platelet-Derived Growth Factor-BB-Stimulated Interleukin-6 Synthesis in Osteoblasts: Suppression of SAPK/JNK
title_full_unstemmed (-)-Epigallocatechin Gallate Reduces Platelet-Derived Growth Factor-BB-Stimulated Interleukin-6 Synthesis in Osteoblasts: Suppression of SAPK/JNK
title_short (-)-Epigallocatechin Gallate Reduces Platelet-Derived Growth Factor-BB-Stimulated Interleukin-6 Synthesis in Osteoblasts: Suppression of SAPK/JNK
title_sort epigallocatechin gallate reduces platelet derived growth factor bb stimulated interleukin 6 synthesis in osteoblasts suppression of sapk jnk
url http://dx.doi.org/10.1155/2008/291808
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